Mechanism of Hepatocyte Apoptosis.

Hepatocyte apoptosis plays important roles in both the removal of external microorganisms and the occurrence and development of liver diseases. Different conditions, such as virus infection, fatty liver disease, hepatic ischemia reperfusion, and drug-induced liver injury, are accompanied by hepatocyte apoptosis. This review summarizes recent research on the mechanism of hepatocyte apoptosis involving the classical extrinsic and intrinsic apoptotic pathways, endoplasmic reticulum stress, and oxidative stress-induced apoptosis. We emphasized the major causes of apoptosis according to the characteristics of different liver diseases. Several concerns regarding future research and clinical application are also raised.

Assessment of liver fibrosis: the relationship between point shear wave elastography and quantitative histological analysis.

BACKGROUND AND AIM: Traditional pathological scoring systems for liver fibrosis progression are predominantly based on the description of architectural changes with no consideration of the amount of collagen fiber deposition. Our purpose was to explore a true histological standard in accordance with the liver stiffness measured by point shear wave elastography (PSWE) in patients with chronic hepatitis B. METHODS: A total of 78 patients with liver neoplasms underwent liver stiffness measurements with PSWE as well as biochemical investigations within 3 days before partial hepatectomy. One tissue section of the liver specimens was stained with HE trichrome and evaluated traditionally with the Scheuer scoring system. The other tissue section was stained with picroSirius red and was evaluated according to the semiquantitative Chevallier et al. scoring system. In addition, this second tissue section was evaluated for the collagen proportionate area (CPA) with computer-assisted digital image analysis. The reproducibility of PSWE technology was explored through the intra-class correlation coefficient of a reliability analysis. RESULTS: The PSWE technology revealed good reproducibility in liver stiffness measurements, and the PSWE values increased with the pathological severity of liver fibrosis on both the Scheuer scoring system and the semiquantitative Chevallier et al. scoring system. PSWE values exhibited more reasonable relationships with CPA (r = 0.628, P = 0.00 < 0.05) than with the Scheuer scoring system (r = 0.473, P = 0.00 < 0.05) or the Chevallier et al. semiquantitative scoring system (r = 0.487, P = 0.00 < 0.05). CONCLUSION: CPA is a better pathological parameter than traditional semiquantitative scoring systems in accordance with liver stiffness measured by PSWE technology.

[Real-time elastography for quantitative assessment of liver fibrosis in a rat model].

OBJECTIVE: To investigate the feasibility of real-time elastography for quantitative evaluation of liver fibrosis in a rat model. METHODS: A total of 70 male Wistar rats were included in the group for dimethylnitrosamine (DMN)-induced liver injury, and 10 saline-injected rats were used as normal control. Hepatic injury was induced by a single intraperitoneal injection of DMN at a dose of 50 mg/kg of body weight. Nine or ten rats in the group with DNM injected and one or two rats in the normal control group were randomly selected and sacrificed at each of the following post-injection time: day 5, 7, 10, 14, 21, 24, and 28. And their livers were taken for pathology analysis. All the rats underwent real-time elastography before sacrificed in order to acquire area ratio of low-strain region (% AREA) and liver fibrosis index (LF index) which were compared with the stage of liver fibrosis and grade of necroinflammatory pathologically. By the different data, Spearman correlation analysis, rank-sum test or receiver operating characteristic curve was used. RESULTS: Among 58 successfully modeled rats, there were nine, 13, 14 and 12 rats of S1, S2, S3 and S4 liver fibrosis on pathology, respectively, which were with or without mild necroinflammatory. The other 10 rats were found to be S0 with severe necroinflammatory. Values of LF index and % AREA both increased with liver fibrosis stage (P less than 0.05). There was certain correlation between LF index and liver fibrosis stage (r=0.643, P=0.000), so was % AREA and liver fibrosis stage (r=0.662, P=0.000). As for LF index, Areas under the receiver operating characteristic curve (Az) was 0.943, 0.890, 0.743 and 0.821 for the diagnosis of hepatic fibrosis S1 or higher, S2 or higher, S3 or higher and S4, respectively; as for % AREA, they were 0.948, 0.883, 0.772 and 0.842, respectively. However, we found a significant difference for LF index or % AREA between S0 with and without severe inflammatory activity rats (P=0.005 and P=0.017). CONCLUSION: Real-time elastography is available for quantitative assessment of liver fibrosis in rats induced by DMN, but severe inflammatory activity can affect its accuracy.

Pathological characteristics, PCNA labeling index and DNA index in prognostic evaluation of patients with moderately differentiated hepatocellular carcinoma.

AIM: To study the relationship between prognosis and pathological characteristics, proliferating cell nuclear antigen labeling index (PCNA-LI) and DNA index (DI) in patients with moderately differentiated hepatocellular carcinoma(HCC). METHODS: 51 cases of moderately differentiated HCC were analyzed with respect to the relation between their clinical follow-up data and pathological characteristics. Meanwhile, PCNA-LI of HCC cells was detected by immunohistochemistry assay and DI was measured by Feulgen staining and automatic image analysis technique. RESULTS: Patients with a single tumor nodule, less than 5 cm in diameter, no tumor emboli, no daughter nodules and necrosis had relatively better prognosis; patients with euploidy HCC had better prognosis than those with aneuploidy; among the aneuploidy patients those with DI<1.5 had better prognosis than the cases with DI>1.5; The higher the PCNA-LI, the worse would be the prognosis. The increase in DI was correlated with the increase in PCNA-LI, and both of them were correlated with the pathological changes of the tumor. CONCLUSION: A composite analysis of the pathological characteristics of tumor tissue, DI and PCNA-LI might be useful in predicting the prognosis of HCC patients.